A major loss of drugs administered to the eye is via the lacrimal drainage system so that only a small fraction of the dose remains in the eye for an extended period of time from a liquid drop formulation.
Different approaches have been taken to slow down this rapid loss of drug by using viscous solutions, gels, ointments and solid inserts.
Improvement in drug delivery has been achieved by these methods especially with the use of solid inserts where a large reduction in dose is possible while achieving the same therapeutic response as a liquid drop which must be administered more frequently and at higher drug concentration.
A principal advantage of the present invention is that it permits the accurate, reproducible unit dosing of a drug or active entity by using volumetric fluid delivery of the dosage prescribed while effecting the ultimate delivery of a semi-solid or rigid gel state. Conventionally, it is not possible to deliver preformed gels from multiple dose containers readily by volumetric means. Gravimetric dosing is thus required to achieve uniform content in delivering reproducible quantities. Conventionally, voids and packing or consolidation problems result when administering semi-solid preparations volumetrically. The present invention provides extremely accurate and uniform content of dose which is critical for many potent drugs.
A significant disadvantage to a solid insert however is that many patients have a difficult time inserting a solid object into the cul-de-sac of the eye and removing said solid object.
Another approach to these problems is to use a formulation which is a liquid at room temperature but which forms a semi-solid when warmed to body temperatures. Such a system has been described in U.S. Pat. No. 4,188,373 using "Pluronic.RTM. polyols" as the thermally gelling polymer. In this system the concentration of polymer is adjusted to give the desired sol-gel transition temperature, that is lower concentration of polymer gives a higher solution-gel (sol-gel) transition temperature. However, with the currently commercially available "Pluronic.RTM." polymers the ability to obtain a gel of the desired rigidity is limited while maintaining the desired sol-gel transition temperature at physiologically useful temperature ranges near 26.degree.-35.degree. C.
Similarly Canadian patent 1072413 which relates to (poloxamer) gel systems with gelling temperatures higher than room temperature uses additives to bring about the gelling characteristics of the polymer which contains therapeutic or other type agents. Also in this Canadian patent "Tetronic.RTM." polymers are used as additive agents rather than the primary polymeric agent as in the instant case.